Ferroptosis in lung cancer: a novel pathway regulating cell death and a promising target for drug therapy DOI Creative Commons
Nan Xing,

Qinyun Du,

Sa Guo

et al.

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: April 1, 2023

Lung cancer is a common malignant tumor that occurs in the human body and poses serious threat to health quality of life. The existing treatment methods mainly include surgical treatment, chemotherapy, radiotherapy. However, due strong metastatic characteristics lung emergence related drug resistance radiation resistance, overall survival rate patients not ideal. There an urgent need develop new strategies or effective drugs treat cancer. Ferroptosis, novel type programmed cell death, different from traditional death pathways such as apoptosis, necrosis, pyroptosis so on. It caused by increase iron-dependent reactive oxygen species intracellular iron overload, which leads accumulation lipid peroxides, thus inducing membrane oxidative damage, affecting normal life process cells, finally promoting ferroptosis. regulation ferroptosis closely physiological it involves metabolism, balance between oxygen-free radical reaction peroxidation. A large number studies have confirmed result combined action cellular oxidation/antioxidant system damage/repair, has great potential application therapy. Therefore, this review aims explore therapeutic targets for clarifying regulatory pathway Based on study ferroptosis, mechanism was understood chemical natural compounds targeting were summarized, with aim providing ideas In addition, also provides basis discovery clinical effectively

Language: Английский

Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis DOI
Xiaoguang Liu, Litong Nie, Yilei Zhang

et al.

Nature Cell Biology, Journal Year: 2023, Volume and Issue: 25(3), P. 404 - 414

Published: Feb. 6, 2023

Language: Английский

Citations

664
Lipid Peroxidation and Iron Metabolism: Two Corner Stones in the Homeostasis Control of Ferroptosis DOI Open Access
Luc Rochette,

Geoffrey Dogon,

Eve Rigal

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 24(1), P. 449 - 449

Published: Dec. 27, 2022

Regulated cell death (RCD) has a significant impact on development, tissue homeostasis, and the occurrence of various diseases. Among different forms RCD, ferroptosis is considered as type reactive oxygen species (ROS)-dependent regulated necrosis. ROS can react with polyunsaturated fatty acids (PUFAs) lipid (L) membrane via formation radical L• induce peroxidation to form L-ROS. Ferroptosis triggered by an imbalance between hydroperoxide (LOOH) detoxification iron-dependent L-ROS accumulation. Intracellular iron accumulation are two central biochemical events leading ferroptosis. Organelles, including mitochondria lysosomes involved in regulation metabolism redox In this review, we will provide overview peroxidation, well key components ferroptotic cascade. The main mechanism that reduces ability glutathione (GSH). GSH, tripeptide includes glutamic acid, cysteine, glycine, acts antioxidant substrate peroxidase 4 (GPX4), which then converted into oxidized (GSSG). Increasing expression GSH inhibit We highlight role xc- GSH-GPX4 pathway regulate system xc-, composed subunit solute carrier family members (SLC7A11 SLC3A2), mediates exchange cystine glutamate across plasma synthesize GSH. Accumulating evidence indicates requires autophagy machinery for its execution. Ferritinophagy used describe removal major storage protein ferritin machinery. Nuclear receptor coactivator (NCOA4) cytosolic bind subsequent degradation ferritinophagy. During ferritinophagy, stored released becomes available biosynthetic pathways. dysfunctional response implicated variety pathological conditions. inducers or inhibitors targeting redox- metabolism-related proteins signal transduction have been developed. simultaneous detection intracellular extracellular markers may help diagnose treat diseases related damage.

Language: Английский

Citations

377
The cell biology of ferroptosis DOI
Scott J. Dixon, James A. Olzmann

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(6), P. 424 - 442

Published: Feb. 16, 2024

Language: Английский

Citations

294
Regulation of ferroptosis by lipid metabolism DOI Creative Commons

Lauren E. Pope,

Scott J. Dixon

Trends in Cell Biology, Journal Year: 2023, Volume and Issue: 33(12), P. 1077 - 1087

Published: July 3, 2023

Language: Английский

Citations

220
System Xc−/GSH/GPX4 axis: An important antioxidant system for the ferroptosis in drug-resistant solid tumor therapy DOI

Feng‐Jiao Li,

Hui‐Zhi Long, Ziwei Zhou

et al.

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 29, 2022

The activation of ferroptosis is a new effective way to treat drug-resistant solid tumors. Ferroptosis an iron-mediated form cell death caused by the accumulation lipid peroxides. intracellular imbalance between oxidant and antioxidant due abnormal expression multiple redox active enzymes will promote produce reactive oxygen species (ROS). So far, few pathways regulators have been discovered regulate ferroptosis. In particular, cystine/glutamate antiporter (System X c − ), glutathione peroxidase 4 (GPX4) (GSH) /GSH/GPX4 axis) plays key role in preventing peroxidation-mediated ferroptosis, because which could be inhibited blocking System axis. This review aims present current understanding mechanism based on axis treatment

Language: Английский

Citations

200
Molecular mechanisms of tumor resistance to radiotherapy DOI Creative Commons
Yu Wu, Yingqiu Song, Runze Wang

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: June 15, 2023

Abstract Background Cancer is the most prevalent cause of death globally, and radiotherapy considered standard care for solid tumors, including lung, breast, esophageal, colorectal cancers glioblastoma. Resistance to radiation can lead local treatment failure even cancer recurrence. Main body In this review, we have extensively discussed several crucial aspects that resistance therapy, radiation-induced DNA damage repair, cell cycle arrest, apoptosis escape, abundance stem cells, modification cells their microenvironment, presence exosomal non-coding RNA, metabolic reprogramming, ferroptosis. We aim focus on molecular mechanisms in relation these discuss possible targets improve outcomes. Conclusions Studying responsible its interactions with tumor environment will help responses radiotherapy. Our review provides a foundation identify overcome obstacles effective

Language: Английский

Citations

200
Metabolism, metabolites, and macrophages in cancer DOI Creative Commons
Mengyuan Li, Yuhan Yang,

Liting Xiong

et al.

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: July 25, 2023

Abstract Tumour-associated macrophages (TAMs) are crucial components of the tumour microenvironment and play a significant role in development drug resistance by creating an immunosuppressive microenvironment. Macrophages essential both innate adaptive immune systems contribute to pathogen regulation organism homeostasis. Macrophage function polarization closely linked altered metabolism. Generally, M1 rely primarily on aerobic glycolysis, whereas M2 depend oxidative Metabolic studies have revealed that metabolic signature TAMs metabolites regulate TAMs. However, precise effects reprogramming tumours remain incompletely understood. In this review, we discuss impact pathways macrophage as well potential strategies for metabolism cancer treatment.

Language: Английский

Citations

154
Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies DOI Creative Commons
Qian Zhou,

Yu Meng,

Daishi Li

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 8, 2024

Ferroptosis is a non-apoptotic form of regulated cell death characterized by the lethal accumulation iron-dependent membrane-localized lipid peroxides. It acts as an innate tumor suppressor mechanism and participates in biological processes tumors. Intriguingly, mesenchymal dedifferentiated cancer cells, which are usually resistant to apoptosis traditional therapies, exquisitely vulnerable ferroptosis, further underscoring its potential treatment approach for cancers, especially refractory cancers. However, impact ferroptosis on extends beyond direct cytotoxic effect cells. induction not only inhibits but also promotes development due negative anticancer immunity. Thus, comprehensive understanding role crucial successful translation therapy from laboratory clinical applications. In this review, we provide overview recent advancements cancer, covering molecular mechanisms, functions, regulatory pathways, interactions with microenvironment. We summarize applications immunotherapy, radiotherapy, systemic therapy, well inhibition various conditions. finally discuss markers, current challenges future directions cancer.

Language: Английский

Citations

153
SLC7A11 expression level dictates differential responses to oxidative stress in cancer cells DOI Creative Commons
Yuelong Yan, Hongqi Teng, Qinglei Hang

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: June 21, 2023

The cystine transporter solute carrier family 7 member 11 (SLC7A11; also called xCT) protects cancer cells from oxidative stress and is overexpressed in many cancers. Here we report a surprising finding that, whereas moderate overexpression of SLC7A11 beneficial for treated with H2O2, common inducer, its high dramatically increases H2O2-induced cell death. Mechanistically, uptake combination H2O2 treatment results toxic buildup intracellular other disulfide molecules, NADPH depletion, redox system collapse, rapid death (likely disulfidptosis). We further show that promotes tumor growth but suppresses metastasis, likely because metastasizing expression are particularly susceptible to stress. Our findings reveal level dictates cells' sensitivity suggests context-dependent role biology.

Language: Английский

Citations

146
The roles of ferroptosis in cancer: Tumor suppression, tumor microenvironment, and therapeutic interventions DOI Open Access
Guang Lei, Li Zhuang, Boyi Gan

et al.

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(4), P. 513 - 534

Published: April 1, 2024

Language: Английский

Citations

116